We are making a major effort to develop the utility of mass spectrometry to assist in the definition of integral membrane proteins and (especially ion channels) at atomic resolutions using diffraction methods. Currently, the structure effort consists of three components (a) work on high-level expression and purification of ion channels, (b) X-ray crystallographic studies of ion channel domains and (c) studies of toxins that bind specifically to ion channels. Our goal is to obtain high-resolution structures of the full, integral membrane ion channel through X-ray crystallography. By combining the exquisitely detailed functional information obtainable using patch-recording methods with mutational studies and three-dimensional structural data from X-ray crystallography, the central questions concerning the mechanisms of ion channel function can be answered. Mass spectrometry is beginning to have a major impact in facilitating this work. Three publications have resulted from this work D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. Mackinnon, "The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity" Science 280, (1998) 69-77. R. Mackinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait "Structural Conservation in Prokaryotic and Eukaryotic Potassium Channels" Science 280 (1998) 106-109. J.H. Morais Cabral, A. Lee, S. Cohen, B.T. Chait, M. Li, R. Mackinnon "Structure of the HERG potassium channel amino-terminal domain definition of a structural family of PAS domains" Cell in press.